Examination of Lyt differentiation markers on thymocytes during murine ontogeny has led to a revised scheme of thymocyte differentiation. This scheme proposes 2 independent precommitted lineages of thymic precursor cells and a site-specific inductive signal for functional and phenotypic differentiation. Fetal thymus transplantation data supported this concept and transplants into chimeras and nude mice demonstrated a disparity between the genetic expression of Lyt markers that are associated with functional subsets of interactive cells and the MHC markers, which on thymocytes, appeared to be expressed according to their thymic environment. Positive selection for Lyt 2 antigen has allowed the separation of the functional lineages for helper T cells, cytotoxic T cells and synergistic interactive T cells and thymus subsets involved in mixed lymphocyte and graft versus host reactions.